BackgroundDutch practice nurses sub-optimally adhere to evidence-based smoking cessation guidelines. Web-based computer-tailoring could be effective in improving their guideline adherence. Therefore, this paper aims to describe the development of a web-based computer-tailored program and the design of a randomized controlled trial testing its (cost-)effectiveness. MethodsTheoretically grounded in the I-Change Model and Self-Determination Theory, and based on the results of a qualitative needs assessment among practice nurses, a web-based computer-tailored program was developed including three modules with tailored advice, an online forum, modules with up-to-date information about smoking cessation, Frequently Asked Questions (FAQs) and project information, and a counseling checklist. The program's effects are assessed by comparing an intervention group (access to all modules) with a control group (access to FAQs, project information and counseling checklist only). Smoking cessation guideline adherence and behavioral predictors (i.e. intention, knowledge, attitude, self-efficacy, social influence, action and coping planning) are measured at baseline and at 6- and 12-month follow-up. Additionally, the program's indirect effects on smokers' quit rates and the number of quit attempts are assessed after 6 and 12months. DiscussionThis paper describes the development of a web-based computer-tailored adherence support program for practice nurses and the study design of a randomized controlled trial testing its (cost-)effectiveness. This program potentially contributes to improving the quality of smoking cessation care in Dutch general practices. If proven effective, the program could be adapted for use by other healthcare professionals, increasing the public health benefits of improved smoking cessation counseling for smokers.